Human immunodeficiency virus, type 1 (HIV-1) infection is a life-threatening and serious disease of major public health significance, with approximately 35 million people infected worldwide (Joint United Nations Programme on HIV/AIDS (UNAIDS). Global report: UNAIDS report on the global AIDS epidemic, 2013). Standard of care for the treatment of HIV-1 infection uses combination antiretroviral therapy (ART) to suppress viral replication to below detectable limits, increase CD4 cell counts, and halt disease progression.
There is also a need for medications to serve populations with limited treatment options (e.g., children, women, and the elderly). In certain situations, these populations may have difficulty maintaining treatment because of pill burden (number of pills to take each day, as well as different combinations of pills) or the size of the pills themselves, once they are coformulated into a multidrug composition. For example, there is currently no fixed dose combination registered for once a day dosing (i.e., QD) for very young children (e.g., younger than age 12 years).
A goal of antiretroviral therapy is to achieve viral suppression in the HIV infected patient. Treatment guidelines published by the United States Department of Health and Human Services provide that achievement of viral suppression requires the use of combination therapies, i.e., several drugs from at least two or more drug classes. In addition, decisions regarding the treatment of HIV infected patients are complicated when the patient requires treatment for other medical conditions (e.g., metformin, rifampin, HCV antivirals, hormonal contraceptives, etc.). Because the standard of care requires the use of multiple different drugs to suppress HIV, as well as to treat other conditions the patient may be experiencing, the potential for drug-drug interaction is a criterion for selection of a drug regimen. As such, there is a need for antiretroviral therapies having a decreased potential for drug-drug interactions (e.g., those that affect transporters (e.g., OCT-2) or activate receptors (e.g., PXR).